Chromosomal anomalies cause various disorders. Anomalies that affect autosomes (the 22 paired chromosomes that are alike in males and females) are more common than those that affect sex chromosomes (X and Y).

Chromosomal abnormalities fit into several categories but broadly may be considered as numerical or structural.

Numerical abnormalities include

Trisomy (an extra chromosome)

Monosomy (a missing chromosome)

Structural abnormalities include

Translocations (anomalies in which a whole chromosome or segments of chromosomes inappropriately join with other chromosomes)

Deletions and duplications of various chromosomes or parts of chromosomes

Terminology

Some specific terms from the field of genetics are important for describing chromosomal anomalies:

Aneuploidy: The most common chromosomal abnormality caused by an extra or missing chromosome.

Karyotype: The full set of chromosomes in a person's cells.

Genotype: The genetic constitution determined by the karyotype.

Phenotype: The person's clinical findings including outward appearance—the biochemical, physiologic, and physical makeup as determined by the genotype and environmental factors (see Overview of Genetics ).

Mosaicism: The presence of ≥ 2 cell lines differing in genotype in a person who has developed from a single fertilized egg.

Diagnosis

Chromosomal analysis

Banding

Karyotype analysis

Chromosomal microarray analysis

Lymphocytes are typically used for chromosomal analysis, except prenatally, when amniocytes or cells from placental chorionic villi are used (see Amniocentesis). A karyotype analysis involves blocking cells in mitosis during metaphase and staining the condensed chromosomes. Chromosomes from single cells are photographed, and their images are arranged, forming a karyotype.

Several techniques are used to better delineate the chromosomes:

In classical banding (eg, G [Giemsa]-, Q [fluorescent]-, and C-banding), a dye is used to stain bands on the chromosomes.

High-resolution chromosome analysis uses special culture methods to obtain a high percentage of prophase and prometaphase spreads. The chromosomes are less condensed than in routine metaphase analysis, and the number of identifiable bands is expanded, allowing a more sensitive karyotype analysis.

Chromosomal microarray analysis (CMA, also called array comparative genomic hybridization) is a single-step technique that allows the entire genome to be scanned for chromosome dosage abnormalities, including increases (duplications) or decreases (deletions), which may be suggestive of an unbalanced translocation. Single nucleotide polymorphism (SNP) microarray analysis has the additional ability to detect regions of homozygosity, which may be seen in cases where parents share common ancestry (consanguinity), and also when there is uniparental disomy (UPD, ie, both of a pair of chromosomes inherited from one parent). It is important to note that CMA does not detect balanced rearrangements (eg, translocations, inversions) that are not associated with deletions and duplications.

Screening

Recently, noninvasive prenatal screening (NIPS) methods have been developed in which cell-free fetal DNA sequences obtained from a maternal blood sample are used for prenatal screening for trisomy 21 ( Down syndrome), trisomy 13, and trisomy 18 and sex chromosome aneuploidy. Although NIPS has good sensitivity and specificity for some chromosomal abnormalities, it is recommended that the results be confirmed using a diagnostic test. More recently, NIPS has been used as a screening test for common microdeletion syndromes (eg, 22q11 deletion); however, the sensitivity and specificity are still relatively low.

Last full review/revision March 2016 by Nina N. Powell-Hamilton, MD, FAAP, FACMG

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